1. Field of the Invention
The present invention generally relates to an apparatus and a method for administering a focused energy treatment to a limited, defined area of a patient's body. The energy treatment can be delivered by the use of one or more energy applicators. The energy applicators can be used to trigger the release of active agents such as pharmaceutically active agents, nutritional agents, diagnostic agents, cosmetic agents, imaging agents, polynucleotides, and the like from liposomes and/or nanoparticles, in particular thermosensitive liposomes or nanoparticles, for the treatment of cancerous, precancerous, and benign lesions, as well as infectious diseases. The energy applicators can also be used to activate thermo-activated drugs, genes, and viral vectors for treatment of the same disease states.
2. Description of the Prior Art
In order to treat a specific treatment site, such as liver, prostate, breast, head and neck, bone, lungs, brain, pancreas, kidney, thyroid, esophageal or other localized solid or defused neoplasms, lesions and tumors, prior art methods have used focused heating devices such as Radio Frequency Ablation (RFA), Microwave Ablation (MA), Laser Ablation (LA), Ultrasound Ablation (UA), High Intensity Focused Ultrasound (HIFU), or focused microwaves (FM) used as a single modality. The previous uses of these treatments were limited in focus to small effective treatment regions. Recurrent tumors often occurred at the margins of a previously treated tumor. There may be ineffective cold spots throughout the treatment zone due to the non-homogeneous nature of these previous heating methods. The use of modalities such as RFA can indeed effectively heat a small defined area of tissue, but this area is limited to tissue in close proximity to a deployed heating antenna. This area is usually only within 1 to 2 centimeters of the heating antenna. Prior heat treating apparatuses have resulted in unsatisfactory tumor control, generally limited to the immediate center of the treatment site. As a consequence, significant tumor recurrence or continued growth of the cancerous tumors are common. Accordingly, there is a major need to increase the therapeutic kill zone over that of the single heat modalities currently employed.
One of the major uses for the above-described heating devices is for the treatment of hepatocellular carcinoma (HCC). Hepatic tumors are either primary or secondary (e.g., metastatic liver cancer (MLC)) and are a substantial medical problem both in the United States and worldwide. The worldwide annual mortality as a result of HCC is estimated to be approximately 1,000,000 persons.
Generally, chemotherapy and radiation therapy are ineffective for treatment of hepatic tumors and certain localized tumors where the above heating modalities are used. The gold standard for the treatment of liver tumors and many solid localized tumors is the surgical resection of the tumor. Unfortunately, less than 20% of patients of primary or secondary liver tumors are eligible for surgical resection due to tumor size. This is also the case where solid tumors have advanced in size, so that it may not be possible to remove the tumor from the organ without compromising the well being of the patient. Even with surgical resection, 5 year survival rates are less than 30%. The outlook is less favorable for patients with unresectable hepatic tumors. Thus, there is a major need for a more effective treatment option for both resectable and unresectable tumors.
Radio Frequency ablation for the treatment of liver cancer was first investigated in the early 1990s. Since that time RFA has quickly become one of the most frequently used minimally invasive treatments for HCC and MLC. There are numerous RFA devices commercially available worldwide to create the thermal energy that ablate the cancer cells. The three primary RFA devices utilized in the U.S. are those made by RITA Medical Systems, Mountain View, Calif.; Radio-therapeutics, Mountain View, Calif.; and Radionics, Burlington, Mass. The power sources of the three devices are very similar in usage, but the RITA Medical Systems and the Radio-therapeutics devices have an umbrella or “Christmas tree” configuration while the Radionics device uses a cool tip single, or multiple, needle design. The RITA Medical Systems device uses a temperature feedback control to terminate the treatment; whereas, the other two employ impedance feedback control. The clinical applications placing the RFA probes in the proximity of the tumor can be performed by open surgery or laproscopically, generally administered by a surgeon, or using a percutaneous treatment which is generally administered by interventional radiologists.
However, regardless of which RFA probes are used or which method of clinical application is used, the RFA treatments are best suited for smaller lesions less than 3 cm in diameter. Thus, all of the devices have similar limitations in the ability to effectively treat larger lesions, especially viable cancer cells in the margins of the lesion. The “margins” are defined by the area outside the solid tumor. The margins outside the boundary area of the tumor in most cases can be up to 2 cm in width. It is desirable to attempt to create tumor-free margins beyond the imaged tumor lesion of 1 cm or greater; however, RFA is often limited in its ability to produce such consistent margins especially for tumors with a maximum diameter greater than 3 cm. As a result, viable tumor cells are left within such margins (or the area between overlapping ablation zones) where tissue is heated above 40° C., but not to the necessary thermal ablation range (e.g., generally greater than 50° C.).
As a result, known RFA devices are only effective in limited areas that can be heated to high enough temperatures; generally greater than 50° C., and sometimes to temperatures greater than 80° C., in order to ablate the viable cancer. The high temperature makes it difficult to prevent damage to surrounding non-cancerous tissues. That is, it is difficult to heat the cancer cells at the margins to greater than 50° C. to kill the diseased tissue and at the same time avoid damaging the surrounding non-cancerous tissue.
High-energy Intensity Focused Ultrasound is another focused heating device. HIFU directs ultrasound to a focused region in order to achieve the temperature required to ablate diseased tissue in the targeted region. HIFU uses ultrasound thousands of times more powerful than that used for imaging. Several HIFU systems are clinically available (Ablatherm from EDAP-Technomed, Lyon, France and Sonablate from Focus Surgery, Indianapolis, Ind.), and several systems are under development in China, Europe, and the USA. Treatment applications have included localized prostate cancer, liver cancer, and benign breast and uterine tumors. With regard to the treatment of prostate tumors, these systems may be less invasive than surgery, cyroblation, or seed implants, but the use of HIFU has also been associated with adverse effects, such as incontinence, recto-urethral fistulas, edema, and chronic necrotic debris and infection. In addition, due to the time taken to treat using the pinpoint focus of HIFU and limitations on the size of the treatment zone, complete ablation and thus control of the tumor will be very difficult to achieve with these known systems. HIFU has also been used for other localized cancers; however, it has only achieved marginal success due to difficulty of use, limited size of ablation area, and difficulty of focusing and directing the energy to exactly where it is required.
Other technologies, such as lasers as developed by Indigo and Johnson & Johnson, transurethral incision of the prostate (TULIP), and visual laser ablation (VLAP), have similar limitations and clinical shortcomings to those of RFA. These shortcomings include the limited size of the effective targeted area and potential adverse effects caused by the high intensity heat. The inability to see in real time the amount of heat generated and the actual location of where the greatest amount of heat is generated can lead to significant cell death of the adjacent healthy cells. In addition, heat is distributed non-uniformly within the targeted treatment zone and does not extend effectively to the margins of the lesions or tumors.
Microwave ablation probes have been used to deliver heat to lesions and tumors, but this technology is invasive. This technology is very similar to RFA technologies. To some extent, MA may be limited by the fact that the regions around blood vessels can sometimes act as heat sinks; these heat sinks can result in cool spots that fail to achieve sufficiently high temperature to kill the lesion or tumor. Another potential limitation of MA is that it can take more time to heat a very confined area of lesion or tumor tissue.
Drug therapy is the standard of care (SOC) for the treatment of many cancerous and infectious diseases. The goal of drug therapy is to deliver an adequate dose of a drug to a specific site to be treated without damaging or killing normal cells. Cytotoxic drugs are generally delivered systemically and thus are neither site-specific, nor cell-specific. As a result, the delivery of cytotoxic drugs can damage normal cells and vital organs. To address this problem, several new drugs have been designed to specifically target cancerous cells by binding to tumor cell specific antigens. These drugs are typically very effective because they only kill specific tumor cells which have the targeted cell surface receptors. Furthermore, due to certain physical and physiological limitations, higher and more effective doses of anti-cancer agents are generally not achievable. However, for many localized lesions within organs such as the liver, prostate, lung, esophageal and breast, complete tumor control (including the tumor margins) has not been significantly improved, nor has there been a dramatic increase in survival rates.
With prostate cancer, for example, the goal is to provide an effective treatment to the diseased region within the gland, without causing major adverse events such as incontinence, sterility, pain, impotence or retrograde ejaculation. These adverse events are also a byproduct of surgery, external radiation and implant therapy, cryotherapy, and RFA. Even with thermotherapy, it can be difficult to heat a significant portion of the prostate gland while sparing healthy tissues therein as well as in the surrounding tissues (such as the urethral and rectal walls). Thus, cancer cells in the margins may not be effectively treated. The prostate, which is the most frequently diseased of all internal organs, not only is a site of cancer among older men, but also for benign prostatic hyperplasia (BPH) and acute prostatitis. Recent treatment of BPH includes transurethral microwave thermotherapy in which microwave energy is employed to elevate the temperature of tissue surrounding the prostatic urethra above about 45° C., thereby thermally damaging the tumorous prostate tissue. U.S. Pat. Nos. 5,330,518 and 5,843,144 describe methods of ablating prostate tumorous tissue by transurethral thermotherapy.
There remains a need to better treat diseased tissue to increase the survival rate of patients and decrease the adverse side effects of treatment. A long felt need in the art of cancer treatment exists to provide therapies that treat an entire tumor, including treatment at the margins without damaging normal non-diseased tissue. Methods solving this long felt need could include methods that achieve an increased concentration of a drug localized at the site of treatment. Therapies could be used not only for treatment of cancers, but also other localized disease states as well.